Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Institute for Molecular Virology, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA.
Viruses. 2024 Sep 27;16(10):1528. doi: 10.3390/v16101528.
Retroviral assembly is a highly coordinated step in the replication cycle. The process is initiated when the newly synthesized Gag and Gag-Pol polyproteins are directed to the inner leaflet of the plasma membrane (PM), where they facilitate the budding and release of immature viral particles. Extensive research over the years has provided crucial insights into the molecular determinants of this assembly step. It is established that Gag targeting and binding to the PM is mediated by interactions of the matrix (MA) domain and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PI(4,5)P). This binding event, along with binding to viral RNA, initiates oligomerization of Gag on the PM, a process mediated by the capsid (CA) domain. Much of the previous studies have focused on human immunodeficiency virus type 1 (HIV-1). Although the general steps of retroviral replication are consistent across different retroviruses, comparative studies revealed notable differences in the structure and function of viral components. In this review, we present recent findings on the assembly mechanisms of Human T-cell leukemia virus type 1 and highlight key differences from HIV-1, focusing particularly on the molecular determinants of Gag-PM interactions and CA assembly.
逆转录病毒的组装是复制周期中一个高度协调的步骤。当新合成的 Gag 和 Gag-Pol 多蛋白被引导到质膜（PM）的内叶时，该过程就开始了，在那里它们促进不成熟病毒颗粒的出芽和释放。多年来的广泛研究为该组装步骤的分子决定因素提供了关键的见解。已经确定 Gag 靶向和与 PM 的结合是由基质（MA）结构域和酸性磷脂如磷脂酰肌醇 4,5-二磷酸（PI(4,5)P）的相互作用介导的。这种结合事件，以及与病毒 RNA 的结合，启动了 Gag 在 PM 上的寡聚化，这一过程是由衣壳（CA）结构域介导的。以前的许多研究都集中在人类免疫缺陷病毒 1 型（HIV-1）上。尽管不同逆转录病毒的复制的一般步骤是一致的，但比较研究显示病毒成分的结构和功能存在显著差异。在这篇综述中，我们介绍了人类 T 细胞白血病病毒 1 型组装机制的最新发现，并强调了与 HIV-1 的关键区别，特别关注 Gag-PM 相互作用和 CA 组装的分子决定因素。
